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1.
Ann Ig ; 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37916765

ABSTRACT

Background: The topic of vaccine confidence is increasingly relevant, particularly due to the COVID-19 pandemic and the global distribution of COVID-19 vaccines. This issue is even more critical for students in healthcare settings, given their future role not only as vaccine recipients but also as advocates for vaccination. In light of this, achieving a good level of vaccine acceptance is crucial. Hence, the aim of our study was to evaluate the attitudes and perceptions of healthcare students regarding vaccines and COVID- 19 vaccination. Methods: Medical and pharmaceutical area students attended an Elective Teaching Activity on COVID-19 vaccines and vaccination campaign, organized at the University of Florence (Italy) and participated in filling two anonymous questionnaires. The first questionnaire was submitted before the Elective Teaching Activity was focused on students' attitudes and perceptions toward vaccines. The second questionnaire was designed to evaluate the students' satisfaction with the course topics. Both descriptive and inferential analyses were performed on the results. In addition, the Vaccine Confidence Index was calculated to evaluate the propensity of students toward vaccinations. Results: A total of 423 students attended the Elective Teaching Activity in the early beginnings of 2022. Overall, students have shown greater confidence in vaccines, compared to COVID-19 vaccines, especially as regards the safety profile. Students' Vaccine Confidence Index was very close to 0.25 value, which indicates being in favor of vaccinations. Nevertheless, in the satisfaction questionnaire filled in at the end of the course, the percentage of students in favor of COVID-19 vaccination increased for both medical (from 94% to 99%) and pharmaceutical area students (from 81% to 97%). Conclusions: Our study suggests that educational activities such as this Elective Teaching Activity, could be considered an effective teaching strategy to improve vaccine acceptance rates among students in healthcare settings.

2.
Front Psychiatry ; 14: 1050236, 2023.
Article in English | MEDLINE | ID: mdl-36816403

ABSTRACT

Background: Newborns' deaths and life-threatening conditions represent extremely stressful events for parents and professionals working in NICUs, facilitating the onset of secondary traumatic stress symptoms. The STRONG study aims to better understand the psychological impact on Italian NICUs staff of bereavement care. Methods: The STRONG (STress afteR lOss in NeonatoloGy) study is a cross-sectional study based on a web survey consisted of four sections: sociodemographic, CommuniCARE-Newborn questionnaire, the Maslach Burnout Inventory and the Impact of Event Scale-Revised. Results: 227 NICU workers (42.7% nurses, 23.3% midwives, 22.2% physicians, 11.8% other HCPs) answered the survey. The hardest tasks were "communicating baby's death" and "informing on autopsy results"; 44.7% of HCPs did not receive formal training in communicating bad news, 44.2% 'learned from the field' by watching other colleagues; 41.2% declared that they do not have any communication strategy. More than 90% of professionals thought that training on bereavement care is necessary. The majority of HCPs showed some degree of post-traumatic stress symptoms: 34% medium and 35.3% severe. Professionals with training in bereavement care and/or in communication had less probability to develop stress symptoms. A multivariate analysis showed that higher levels of burnout were associated with 4 or more monthly losses and medium or severe stress symptoms. Having a well-defined communication strategy for breaking bad news was independently associated with a better personal accomplishment. Conclusion: Dealing with newborns' deaths is a highly stressful task; professionals should receive proper support such as debriefing, psychological support and training in order to prevent post-traumatic stress symptoms and reduce professional burnout.

3.
Eur J Clin Pharmacol ; 78(7): 1155-1163, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35484251

ABSTRACT

PURPOSE: To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression. METHODS: We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10. RESULTS: At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09-0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14-0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70-0.96) were associated with a significantly lower risk of AD progression. CONCLUSION: Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage.


Subject(s)
Alzheimer Disease , Acetylcholinesterase/therapeutic use , Alzheimer Disease/diagnosis , Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/therapeutic use , Disease Progression , Humans , Memantine/therapeutic use , Retrospective Studies
4.
J Matern Fetal Neonatal Med ; 34(6): 952-959, 2021 Mar.
Article in English | MEDLINE | ID: mdl-31113267

ABSTRACT

BACKGROUND: Stillbirths affect more than 2.5 million pregnancies worldwide every year and the progress in reducing stillbirth rates is slower than that required by World Health Organization. The aim of the present study was to investigate which factors were associated with stillbirths in a University Hospital in the North of Italy, over a time span of 30 years. The goal was to identify which factors are potentially modifiable to reduce stillbirth rate. METHODS: Retrospective case-control study (358 stillbirths, 716 livebirths) subdivided into two study periods (1987-2006 and 2007-2017). RESULTS: The prevalence of conception obtained by assisted reproductive technologies, pregnancy at advanced maternal age, and complications of pregnancy such as preeclampsia, fetal growth restriction (FGR), and other fetal diseases (abnormal fetal conditions including fetal anemia, fetal hydrops, TORCH infections) increased through the years of the study. Despite a rising prevalence, the last 10 years showed a significant reduction in stillbirths associated with preeclampsia and FGR. Similarly, the risk of stillbirth related to abnormal fetal conditions decreased in the second study period and a history of previous stillbirth becomes a nonsignificant risk factor. CONCLUSIONS: Altogether these results suggest that in pregnancies perceived as "high risk" (i.e. previous stillbirth, preeclampsia, FGR, abnormal fetal conditions) appropriate care and follow-up can indeed lower stillbirth rates. In conclusion, the road to stillbirth prevention passes inevitably through awareness and recognition of risk factors.


Subject(s)
Stillbirth , Case-Control Studies , Female , Humans , Italy/epidemiology , Pregnancy , Retrospective Studies , Risk Factors , Stillbirth/epidemiology
5.
J Matern Fetal Neonatal Med ; 32(1): 125-128, 2019 Jan.
Article in English | MEDLINE | ID: mdl-28868940

ABSTRACT

PURPOSE: Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy, nearly 80% of all the prescription medications during gestation. The use of fosfomycin to treat cystitis in pregnancy generally considered safe and effective. Even though use on antibiotics for urinary tract infections is considered generally safe for the fetus and mothers, this opinion is not based on specific studies monitoring the relationship of among urinary infections, consumption of antibiotics, and pregnancy outcomes. MATERIALS AND METHODS: On this basis we decided to analyze data from the database of our multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken into consideration. RESULTS: Women who have been treated with urinary antibiotics during the pregnancy were 183. With respect to the total number of pregnancies of our sample, these women represented the percentage of 3.49% (187/5362). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight, and neonatal Apgar index did not show any significant difference. At the same time, analysis of data of pregnancy complicancies (such as urgent cesarean delivery, use of general anesthesia, need to induce labor) did not show any difference in women taking fosfomycin during pregnancy and those not taking it. CONCLUSIONS: Our data, based on a large number of pregnancies, confirm the safety use of fosfomycin use in pregnancy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Fosfomycin/therapeutic use , Pregnancy Complications, Infectious/drug therapy , Pregnancy Outcome/epidemiology , Urinary Tract Infections/drug therapy , Adult , Female , Humans , Italy/epidemiology , Pregnancy
6.
BJOG ; 125(2): 193-201, 2018 Jan.
Article in English | MEDLINE | ID: mdl-27905202

ABSTRACT

OBJECTIVE: To assess the frequency of additional care, and parents' perceptions of quality, respectful care, in pregnancies subsequent to stillbirth. DESIGN: Multi-language web-based survey. SETTING: International. POPULATION: A total of 2716 parents, from 40 high- and middle-income countries. METHODS: Data were obtained from a broader survey of parents' experiences following stillbirth. Data were analysed using descriptive statistics and stratified by geographic region. Subgroup analyses explored variation in additional care by gestational age at index stillbirth. MAIN OUTCOME MEASURES: Frequency of additional care, and perceptions of quality, respectful care. RESULTS: The majority (66%) of parents conceived their subsequent pregnancy within 1 year of stillbirth. Additional antenatal care visits and ultrasound scans were provided for 67% and 70% of all parents, respectively, although there was wide variation across geographic regions. Care addressing psychosocial needs was less frequently provided, such as additional visits to a bereavement counsellor (10%) and access to named care provider's phone number (27%). Compared with parents whose stillbirth occurred at ≤ 29 weeks of gestation, parents whose stillbirth occurred at ≥ 30 weeks of gestation were more likely to receive various forms of additional care, particularly the option for early delivery after 37 weeks. Around half (47-63%) of all parents felt that elements of quality, respectful care were consistently applied, such as spending enough time with parents and involving parents in decision-making. CONCLUSIONS: Greater attention is required to providing thoughtful, empathic and collaborative care in all pregnancies following stillbirth. Specific education and training for health professionals is needed. TWEETABLE ABSTRACT: More support for providing quality care in pregnancies after stillbirth is needed. PLAIN LANGUAGE SUMMARY: Study rationale and design More than two million babies are stillborn every year. Most parents will conceive again soon after having a stillborn baby. These parents are more likely to have another stillborn baby in the next pregnancy than parents who have not had a stillborn baby before. The next pregnancy after stillbirth is often an extremely anxious time for parents, as they worry about whether their baby will survive. In this study we asked 2716 parents from 40 countries about the care they received during their first pregnancy after stillbirth. Parents were recruited mainly through the International Stillbirth Alliance and completed on online survey that was available in six languages. Findings Parents often had extra antenatal visits and extra ultrasound scans in the next pregnancy, but they rarely had extra emotional support. Also, many parents felt their care providers did not always listen to them and spend enough time with them, involve them in decisions, and take their concerns seriously. Parents were more likely to receive various forms of extra care in the next pregnancy if their baby had died later in pregnancy compared to earlier in pregnancy. Limitations In this study we only have information from parents who were able and willing to complete an online survey. Most of the parents were involved in charity and support groups and most parents lived in developed countries. We do not know how well the findings relate to other parents. Finally, our study does not include parents who may have tried for another pregnancy but were not able to conceive. Potential impact This study can help to improve care through the development of best practice guidelines for pregnancies following stillbirth. The results suggest that parents need better emotional support in these pregnancies, and more opportunities to participate actively in decisions about care. Extra support should be available no matter how far along in pregnancy the previous stillborn baby died.


Subject(s)
Parents/psychology , Prenatal Care/standards , Stillbirth/psychology , Adult , Developed Countries , Developing Countries , Female , Humans , Internet , Male , Middle Aged , Quality of Health Care , Surveys and Questionnaires , Young Adult
8.
J Pharm Biomed Anal ; 88: 7-15, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24013031

ABSTRACT

The efficiency of 1D and 2D NMR spectroscopy along with HPLC-DAD-MS analyses in characterising the content of a dietary supplement is demonstrated. Experiments directly performed on a lyophilised sample of a commercial product gave details on the quality control of the product. The lack of the marker constituents of some of the declared plant species (Crataegus oxyacantha, Olea europea, Capsella bursa-pastoris and Fumaria officinalis) and the presence of banned adulterants, responsible for the strong antihypertensive effect of the supplement were established. The analyses proved the presence of indole alkaloids belonging to the group of Rauwolfia sp., such as ajmaline, reserpine and yohimbine. Quantitative HPLC analysis showed that the content of reserpine in the product was in the therapeutic range and therefore responsible for the collapses of the patients.


Subject(s)
Antihypertensive Agents/adverse effects , Dietary Supplements/analysis , Drug Contamination , Plant Extracts/analysis , Alkaloids/analysis , Antihypertensive Agents/analysis , Calibration , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Pharmacovigilance , Plant Leaves , Plants, Medicinal , Quality Control , Rauwolfia/metabolism , Technology, Pharmaceutical
10.
Article in English | MEDLINE | ID: mdl-22899959

ABSTRACT

Fennel (Foeniculum vulgare Mill.) mature fruit (commonly known as seeds) and essential oil of fennel are widely used as flavoring agents in food products such as liqueurs, bread, cheese, and an ingredient of cosmetics and pharmaceutical products. Moreover fennel infusions are the classical decoction for nursing babies to prevent flatulence and colic spasm. Traditionally in Europe and Mediterranean areas fennel is used as antispasmodic, diuretic, anti-inflammatory, analgesic, secretomotor, secretolytic, galactagogue, eye lotion, and antioxidant remedy and integrator. Topically, fennel powder is used as a poultice for snake bites. In Asian cultures fennel was ingested to speed the elimination of poisons. As one of the ancient Saxon people's nine sacred herbs, fennel was credited with the power to cure. Fennel was also valued as a magic herb: in the Middle Ages it was draped over doorways on Midsummer's Eve to protect the household from evil spirits. Recently because of estragole carcinogenicity, fennel has been charged to be dangerous for humans especially if used as decoction for babies. But this allegation do not consider the remedy is prepared as a matrix of substances, and recent researches confirm that pure estragole is inactivated by many substance contained in the decoction.

11.
J Clin Pharm Ther ; 37(2): 245-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21569069

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Methotrexate (MTX) is widely used in the management of paediatric cancer with a generally favourable benefit/risk profile. We report an unusual adverse drug reaction with the first course of high-dose MTX in a paediatric patient and review the literature for similar cases. CASE SUMMARY: An 11-year-old boy with small-cell osteoblastic osteosarcoma in the lower limb experienced a case of life-threatening anaphylaxis during the first course of high-dose MTX. The adverse event occurred during the first course, likely due to an immune-mediated mechanism. We postulate that prior antineoplastic treatment might have contributed to the immune response to MTX. WHAT IS NEW AND CONCLUSION: Given that this reaction has rarely been reported, we discuss the present case with a review of other similar cases. Further studies are needed to substantiate this 'signal alarm' for serious MTX-related hypersensitivity reactions.


Subject(s)
Anaphylaxis/chemically induced , Antimetabolites, Antineoplastic/adverse effects , Methotrexate/adverse effects , Anaphylaxis/immunology , Antimetabolites, Antineoplastic/administration & dosage , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Child , Dose-Response Relationship, Drug , Drug Hypersensitivity/etiology , Drug Hypersensitivity/immunology , Humans , Male , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Osteosarcoma/drug therapy , Osteosarcoma/pathology
12.
Pharm World Sci ; 32(2): 200-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20135228

ABSTRACT

OBJECTIVES: To evaluate the type, frequency, severity and predictors of potential Drug-Drug Interactions (DDIs) in a cohort of patients undergoing radiodiagnostic procedures. SETTING: Eight Radiology wards located in Tuscany (Italy). METHODS: All participants exposed to at least two medications were included in the analysis. DDIs were grouped according to their severity as 'minor', 'moderate' or 'major'. A logistic model was used to estimate Odds Ratios and 95% Confidence Intervals for all predictors of potential DDI. MAIN OUTCOME MEASURES: Type and predictors of potential DDI in a cohort of patients undergoing radiodiagnostic procedures. RESULTS: One-thousand-and-two subjects (57.6% females; mean age: 67.3 +/- 12.2) entered the analysis, and 46.1% of them incurred in a potential DDI (78.9% 'moderate' in severity). The combination of allopurinol and ACE-inhibitors was the most frequent (21/153) among major potential DDIs, while steroids were involved in all cases of potential DDI due to premedication. Co-morbidity, number of co-medications, advanced age and premedication use increased the risk of potential DDI; a protective role was found for positive history of allergy. When the analysis was restricted to subjects with premedication (n = 93), only 12.9% of them reported a potential DDI directly attributable to premedication drugs. CONCLUSIONS: Among patients undergoing radiological examination, types and predictors of potential DDIs appeared in agreement with other kind of in-hospital populations. Premedication revealed to be a proxy predictor for potential DDIs. Considering the poor capability of the prescriber in recognizing interactions, their systematic evaluation (using an informatics tool) in patients undergoing radiological examination might be helpful in preventing the occurrence of clinically relevant DDIs.


Subject(s)
Drug Interactions , Magnetic Resonance Imaging , Radiography/methods , Age Factors , Aged , Cohort Studies , Comorbidity , Female , Hospital Administration , Humans , Male , Middle Aged , Polypharmacy , Premedication
14.
J Clin Pharm Ther ; 34(1): 129-32, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19125912

ABSTRACT

We report a case of increase in serum tumour markers CA 125 and CA 19.9 induced by cyclic combined hormone replacement therapy (HRT). A 52-year-old Caucasian post-menopausal woman presented with a slight enlargement of the right ovary and uterine fibromyomatosis. She was taking HRT for 4 years in a cyclic combined regimen of 2 mg oestradiol with 1 mg cyproterone acetate. The serum tumour markers occasionally measured were in normal range except CA 19.9 (997 U/mL; normal values 0.0-37) and CA 125 (85 U/mL; normal values 0.0-35). However, on one occasion, the CA 19.9 and CA 125 were high and then showed persistently high values (1005 and 81.3 U/mL, respectively). Radiodiagnostic investigations excluded any malignancies and a hysteroscopy showed endometrial thickening. After discontinuation of HRT, CA 125 levels returned to normal after 1 month, whereas CA 19.9 took 6 months to do so. Four months after the beginning subsequent therapy with over-the-counter phyto-oestrogens a new serum test showed an increase in CA 19.9 but CA 125 remained within the normal range. Phyto-oestrogen therapy was then interrupted and 1 month later CA 19.9 returned to normal. In this case, cyclic HRT was the probable cause of CA 19.9 and CA 125 increase. Positive dechallenge and subsequent CA 19.9 increase after phyto-oestrogen intake seem to confirm the role of oestrogens as the cause of the endometrial thickening through hormonal imbalance. Increased CA 19.9 and CA 125 levels in benign gynaecological conditions may be a source of misdiagnosis of malignant disease.


Subject(s)
CA-125 Antigen/blood , CA-19-9 Antigen/blood , Estrogen Replacement Therapy/adverse effects , Biomarkers, Tumor/blood , Cyproterone Acetate/administration & dosage , Cyproterone Acetate/adverse effects , Drug Administration Schedule , Drug Combinations , Estradiol/administration & dosage , Estradiol/adverse effects , Female , Humans , Middle Aged , Phytoestrogens/administration & dosage , Phytoestrogens/adverse effects , Postmenopause
15.
J Cell Mol Med ; 12(6A): 2381-94, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18266975

ABSTRACT

In this study we evaluated the effects of the CB1/CB2 cannabinoid receptor agonist CP55, 940 (CP) on antigen-induced asthma-like reaction in sensitized guinea pigs and we tested the ability of the specific CB2 receptor antagonist SR144528 (SR) and CB1 receptor antagonist AM251 (AM) to interfere with the effects of CP. Ovalbumin-sensitized guinea pigs placed in a respiratory chamber were challenged with the antigen given by aerosol. CP (0.4 mg/kg b.wt.) was given i.p. 3 hrs before ovalbumin challenge. Sixty minutes before CP administration, some animals were treated i.p. with either AM, or SR, or both (0.1 mg/kg b.wt.). Respiratory parameters were recorded and quantified. Lung tissue specimens were then taken for histopathological and morphometric analyses and for eosinophilic major basic protein immunohistochemistry. Moreover, myeloperoxidase activity, 8-hydroxy-2-deoxyguanosine, cyclic adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP) levels, and CB1 and CB2 receptor protein expression by Western blotting were evaluated in lung tissue extracts. In the bronchoalveolar lavage fluid, the levels of prostaglandin D2 and tumour necrosis factor-alpha TNF-alpha were measured. Ovalbumin challenge caused marked abnormalities in the respiratory, morphological and biochemical parameters assayed. Treatment with CP significantly reduced these abnormalities. Pre-treatment with SR, AM or both reverted the protective effects of CP, indicating that both CB1 and CB2 receptors are involved in lung protection. The noted treatments did not change the expression of cannabinoid receptor proteins, as shown by Western blotting. These findings suggest that targeting cannabinoid receptors could be a novel preventative therapeutic strategy in asthmatic patients.


Subject(s)
Asthma/prevention & control , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB2/agonists , 8-Hydroxy-2'-Deoxyguanosine , Animals , Antigens/administration & dosage , Asthma/etiology , Asthma/pathology , Asthma/physiopathology , Camphanes/pharmacology , Cyclic AMP/metabolism , Cyclohexanols/pharmacology , DNA Damage/drug effects , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Guinea Pigs , Humans , Leukocytes/drug effects , Leukocytes/pathology , Lung/drug effects , Lung/pathology , Lung/physiopathology , Male , Mast Cells/drug effects , Mast Cells/physiology , Models, Biological , Ovalbumin/immunology , Piperidines/pharmacology , Prostaglandin D2/metabolism , Pyrazoles/pharmacology , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Receptor, Cannabinoid, CB2/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism
17.
Inflamm Res ; 55(7): 261-73, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16955388

ABSTRACT

The double origin of carbon monoxide (CO) as an atmospheric pollutant or as an endogenous gaseous modulator of many pathophysiological processes prompted us to review some aspects of the bad side and of the good side of coin among the pleiotropic effects of CO. On the bad side of the coin, we focus on the interval form in acute CO poisoning, discussing experimental evidence suggesting that the delayed neuropathology after CO poisoning is a free radical-driven event. In this context, we challenge the mandatory place of hyperbaric oxygen therapy (HBO) in CO poisoning as a possible summation of oxy-radicals generated by HBO and the free radical cascade set in motion during the reoxygenation phase of acute CO-poisoning. We also discuss an opposing view, which provides evidence suggesting that HBO therapy actually decreases the load of free radicals in acute CO-poisoning and may be beneficial in preventing delayed neuropsychiatric sequelae.On the good side of the coin, we briefly outline the endogenous generation of CO and the leading role of heme-oxygenases (HO) in relation to the place of CO in biology and medicine. The main focus of this section is on the growing literature on CO and inflammation. Here we report on in-vitro and in-vivo studies on the modulation afforded by exogenously administered/endogenously produced CO in a variety of experimental and clinical settings of inflammation. Our recent studies on experimental models of allergic inflammation are also discussed, and the CO-releasing molecules envisaged as potential anti-inflammatory drugs suitable for clinical use.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Carbon Monoxide/pharmacology , Carbon Monoxide/toxicity , Inflammation/pathology , Neurons/drug effects , Animals , Carbon Monoxide Poisoning , Cell Death , Heme Oxygenase (Decyclizing)/metabolism , Humans , Hyperbaric Oxygenation , Models, Biological , Neurons/pathology
20.
Cell Mol Biol (Noisy-le-grand) ; 51(4): 393-401, 2005 Sep 30.
Article in English | MEDLINE | ID: mdl-16309590

ABSTRACT

The enzymes heme oxygenase (HO) generate carbon monoxide (CO) in living organisms during heme degradation. Carbon monoxide has recently been shown to dilate blood vessels and to possess anti-inflammatory properties. It is also known that nitric oxide (NO) donors ameliorate cardiac ischaemia-reperfusion injury in experimental models of global or focal ischaemia-reperfusion (FIR). The two gaseous mediators share the same mechanism of action via the stimulation of soluble guanylyl cyclase and the increase in cellular levels of cyclic GMP. We studied the effects of manipulating the HO system and the possible interaction between CO and NO in an experimental in vivo model of FIR in the rat heart. FIR-subjected rats had necrotic area in the left ventricle, ventricular arrhythmias and a shortening of survival time in comparison to sham-operated animals. Resident mast cells underwent a heavy degranulation, malonyldialdehyde was produced by myocardial cell membranes, and tissue calcium levels were increased. High levels of myeloperoxidase were also detected, suggesting a FIR-related inflammatory process. In animals pre-treated with the HO-1 inducer, hemin, all the biochemical and morphometric markers of FIR were minimized or fully abated. Consistently, the biochemical and morphometric markers of FIR were reversed in rats treated with the HO-1 blocker, ZnPP-IX, prior to hemin administration. Pre-treatment with hemin significantly increases the expression and activity of both cardiac HO-1 and iNOS, suggesting that CO and NO cooperate in the cardioprotective effect against FIR-induced damage, and that there is a therapeutic synergism between NO-donors and CO-releasing molecules, via the common stimulation of increase in cGMP levels and decrease in calcium overload.


Subject(s)
Disease Models, Animal , Heart Injuries/enzymology , Heart Injuries/pathology , Heme Oxygenase (Decyclizing)/metabolism , Myocardial Reperfusion Injury/enzymology , Myocardial Reperfusion Injury/pathology , Nitric Oxide Synthase/metabolism , Animals , Bilirubin/metabolism , Calcium/metabolism , Cyclic GMP/metabolism , Enzyme Induction , Male , Malondialdehyde/metabolism , Mast Cells , Peroxidase/metabolism , Rats , Rats, Wistar , Survival Rate , Time Factors
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